The goal of this project is to map and identify genes for syndromic and nonsyndromic forms of herditary deafness. Linkage analyses are being conducted using large pedigrees segregating non-syndromic or syndromic forms of deafness. If linkage to a known syndromic, DFNA (dominant) and DFNB (recessive) locus in large families is excluded, we initiate a genome-wide screen. The chromosomal map locations of novel deafness loci are refined prior to initiating positional cloning strategies to identify the genes responsible for hearing loss. Additional families with dominant and recessive modes of inheritance with profound congenital or progressive hearing loss are being ascertained with the goal of mapping and cloning additional novel genes that are necessary for hearing and/or maintenace of the auditory system. We are also continuing to ascertain families, mapping loci and identifying genes for Usher syndrome. The defining clinical features of Usher syndrome are hearing loss and progressive loss of vision due retinitis pigmentosa. During the past year this strategy has allowed us to map a novel locus for type 1 Usher syndrome (USH1H), to identify mutations of LRTOMT as the cause of nonsyndromic deafness DFNB63 and, in collaboration with Dr. Hannie Kremer, to identify mutations of ESRRB encoding estrogen-related receptor beta, as the cause of nonsyndromic deafness DFNB35.